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Decitabine reverses TGF-β1-induced epithelial–mesenchymal transition in non-small-cell lung cancer by regulating miR-200/ZEB axis

Authors Zhang N, Liu Y, Wang Y, Zhao M, Tu L, Luo F

Received 2 December 2016

Accepted for publication 31 January 2017

Published 28 March 2017 Volume 2017:11 Pages 969—983


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Qiongyu Guo

Nan Zhang,* Yanyang Liu,* Yuyi Wang, Maoyuan Zhao, Li Tu, Feng Luo

Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Objective: Epithelial–mesenchymal transition (EMT) is a crucial driver of tumor progression. Tumor growth factor-beta 1 (TGF-β1) is an important factor in EMT induction in tumorigenesis. The targeting of EMT may, therefore, represent a promising approach in anticancer treatment.
Methods: In this study, we determined the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-β1-induced EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed the involvement of the miR-200/ZEB axis.
Results: Decitabine reversed TGF-β1-induced EMT in PC9 cells, but not in A549 cells. This phenomenon was associated with epigenetic changes in the miR-200 family, which regulated EMT by altering the expression of ZEB1 and ZEB2. TGF-β1 induced aberrant methylation in miR-200 promoters, leading to EMT in PC9 cells. Decitabine attenuated this effect and inhibited tumor cell migration in vitro and in vivo. In A549 cells, however, neither TGF-β1 nor decitabine exhibited an effect on miR-200 promoter methylation.
Conclusion: Our findings suggest that epigenetic regulation of the miR-200/ZEB axis is responsible for EMT induction by TGF-β1 in PC9 cells. Decitabine inhibits EMT in NSCLC cell PC9 through its epigenetic-based therapeutic activity.

Keywords: DNA methyltransferase inhibitor, EMT, miRNA, epigenetics, NSCLC

Corrigendum for this paper has been published

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